It is proposed to continue a research project designed to yield information about DNA base damage and its effects in vivo. Undamaged thymine bases, found to be released from intact E. coli C cells during Co60 gamma-irradiation, will be quantitated with regard to radiation dose and post-irradiation holding time. Specific thymine base damage products which remain in the DNA0unitl it is removed from the cells and hydrolyzed enzym@tically will be quantitated more accurately as a function of radiation dose, level of survival, and ability of various selected bacterial strains to repair this damage. The effects of radiosensitizers and radioprotectors on the quantities of undamaged thymine released and thymine base damage prod@cts retained in the DNA will be investigated. In vivo studies recently initiated on the release of undamaged cytosine and adenine bases and on damaged cytosine and adenine bases retaind in the DNA will be expanded. The information obtained from this project will greatly increase the amount of substantive data available on DNA0base destruction as it occurs in vivo and will allow, for the first time, a direct assessment of the applicability of much of the previous research on the radiation chemistry of DNA and its constituents in vitro to actual in vivo damage.